Cellules myeloides suppressives

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Presentation transcript:

Cellules myeloides suppressives M1 – UE9 29 Octobre 2015 Mikael ROUSSEL mikael.roussel@chu-rennes.fr

Hematopoiese Bone Marrow Lymph FL Node Blood Blood Tissues MPP : progéniteur multipotent CMLP : progéniteur myélo-lympho commun CLP : progéniteur lymphoïde commun CMP : progéniteur myéloïde commun CDP : progéniteur DC commun GMP : progéniteur granuleux et macrophages MCP progéniteur mastocytes MDP : progéniteur macrophage et DC MEP : progéniteur megacaryocyte et érythroïde Blood Blood Tissues Gabrilovich, Nat Rev Immunol, 2012

Microenvironment and cancer FL Wolf-Herman, Nat Rev Cancer, 2012 De Visser, Nat Rev Cancer, 2006

Microenvironment and cancer FL Narendra, Inflamm Res, 2013

Populations myéloides suppressives Suppressive = régulatrice = immunomodulatrice Supprime la réponse T et NK Large family of tolerogenic cells: Treg, Breg, tolerogenic DC, MSC, regulatory macrophages, MDSC turn-on / turn-off Complex regulation Impair T effector and NK functions IL-10, TGF-b aa depletion (IDO, Arginase)

Changes that occur in myeloid cells in cancer Monocyte -in blood -APC ((<DC) -Phagocytosis -Cytokine production -migrate to the tissue DC : -APC -activate T -link between innate and adaptative Macrophage -in tissue -APC -Phagocytosis -Inflammation/anti-inflammation Gabrilovich, Nat Rev Immunol, 2012

Changes that occur in myeloid cells in cancer MDSC: 1-Immature state 2-Myeloid origin 3-Supress T-cell responses 4-Regulate innate immune responses: modulation the cytokine production of macrophages 5-Non-immunological functions: promote angiogenesis promote metastasis Gabrilovich, Nat Rev Immunol, 2012

Changes that occur in myeloid cells in cancer Physiological paths Cancer/Sepsis Support tumor growth suppress anti-tumor immunity Support angiogenesis/metastasis soluble factors Potential immunotherapy target Gabrilovich, Nat Rev Immunol, 2012

Signaling pathways involved in MDSC expansion Inhibition of diff Stimulation of myelopoiesis Gabrilovich, Nat Rev Immunol, 2009

Signaling pathways involved in MDSC activation Gabrilovich, Nat Rev Immunol, 2009